Degeneracy in hippocampal physiology and plasticity

Abstract

Degeneracy, defined as the ability of structurally disparate elements to perform analogous function, has largely been assessed from the perspective of maintaining robustness of physiology or plasticity. How does the framework of degeneracy assimilate into an encoding system where the ability to change is an essential ingredient for storing new incoming information? Could degeneracy maintain the balance between the apparently contradictory goals of the need to change for encoding and the need to resist change towards maintaining homeostasis? In this review, we explore these fundamental questions with the mammalian hippocampus as an example encoding system. We systematically catalog lines of evidence, spanning multiple scales of analysis, that demonstrate the expression of degeneracy in hippocampal physiology and plasticity. We assess the potential of degeneracy as a framework to achieve encoding and homeostasis without cross-interferences, and postulate that multiscale parametric and interactional complexity could establish disparate routes towards accomplishing these conjoint goals. These disparate routes then provide several degrees of freedom to the encodinghomeostasis system in accomplishing its tasks in an input-and state-dependent manner. Finally, the expression of degeneracy spanning multiple scales offers an ideal reconciliation to several outstanding controversies, through the recognition that the seemingly contradictory disparate observations are merely alternate routes that the system might recruit towards accomplishment of its goals. Juxtaposed against the ubiquitous prevalence of degeneracy and its strong links to evolution, it is perhaps apt to add a corollary to Theodosius Dobzhansky's famous quote and state "nothing in physiology makes sense except in the light of degeneracy".peer-reviewed)

Degeneracy in the emergence of spike-triggered average of hippocampal pyramidal neurons

“…This demonstration was constrained biophysically by the ion channel gating and kinetic properties and physiologically validated by STA and excitability measurements, all of which were obtained from hippocampal pyramidal neurons. Our results suggest that hippocampal neurons have significant degrees of freedom to achieve the specific encoding and homeostasis targets without cross-interferences in these processes 8 . Although our conclusions could potentially extend to other neuronal subtypes, such extrapolations should specifically account for biophysical characteristics of ion channels expressed in those neurons and the STA and excitability measurements from there as well.…”

“…This error signal is then employed by the system to organize its parametric space to achieve a given function, with the specific structural components chosen to achieve the function determined by the internal state of the system, neuromodulatory tones and the nature of afferent signals. A specific instance of such a broad description is with reference to the role of calcium homeostasis in maintaining channel densities through calcium-dependent transcription that is dependent on a calcium error signal 7,8,10,15,44 . Here, it has been shown that the solutions achieved by neurons and their networks could recruit disparate channels and receptors depending on the specific components of the network and the nature of afferent signals 15,44 .…”

“…For instance, there are scenarios where calcium homeostasis is maintained without homeostasis of firing rate or firing pattern, or scenarios where one model measurement is observed to match electrophysiological counterparts but others don't 15,44 . This dissociation in different modes of homeostasis implies that models have to explicitly account for different measurements, and tuning of one of them doesn't necessarily maintain all measurements at physiological levels 8,15 . Such dissociation also implies that multi-parametric stochastic searches would, in general, yield lesser valid models as additional physiological objectives are added to the validation process (e.g., Supplementary Fig.…”

“…Does this imply that the degeneracy reported here would reduce as additional physiological constraints are included to the validation process? Degeneracy refers to the ability of different structural components to elicit similar function, and is by definition specific to the function in hand 1,8 . Degeneracy also implies that the same structure could be involved in the execution of a different function under a different context.…”

“…This explosion in degrees of freedom then provides additional routes to fulfilling the multiple functional constraints (either in the same context or under different contexts). Finally, the cell-to-cell and animal-to-animal variability in constituent components, despite the expression of similar functional outcomes, provide lines of evidence for the expression of degeneracy in biological systems 1,7,8,16,17,52 .…”